The proposed studies continue to address the hypotheses that the monocyte/macrophage is the major cellular component controlling the tissue/material inflammatory, foreign body, and wound healing responses, and that monocyte, macrophage, and foreign body giant cell (FBGC) adhesion receptor/biomaterial surface interactions and cytokine production are differentially affected by material surface properties. In the present application, our objectives have been significantly expanded to encompass the influences of biomaterial surface chemistries or inflammatory monocyte/macrophage recruitment, chemokine and matrix proteinase production, matrix deposition mechanisms of apoptosis, and the responses of wound healing cells. Therefore, the specific aims of this project have been designed to address the effects of material surface chemistry on major biological response mechanism, that represent multiple and interrelated aspects of the foreign body reaction. The specific aims of the project are: 1) To determine the mechanisms of monocyte/macrophage recruitment, activation, and production of chemokines and cytokines; 2) To elucidate the mechanisms of monocyte, macrophage, and FBGC adhesion, matrix production, ant matrix proteolysis; 3) To investigate the mechanisms of monocyte/macrophage-derived chemokine, cytokine, and matrix/matrix proteinase-mediated wound healing responses; and 4) To determine the material-dependent cellular mechanisms by which the presence of adherent macrophages and FBGC can be controlled with apoptosis. Based on the results of our previous studies, four different model surface-modified material systems for inflammatory and wound healing interactions have been selected for this investigation. These material systems provide for a wide range of surface chemistries currently being used in clinical devices and prostheses as well as in the development ot new materials and devices. The model surface-modified systems are: 1) RGD-modified surfaces; 2) photopolymerized graft polymers; 3) silane-modified molecularly engineered surfaces; and 4) temperature responsive surfaces. Correlative in vitro cell culture and in vivo murine cage and subcutaneous implant models will be utilized to address the hypotheses and specific aims with state-of-the-art gene expression array analysis, flow cytometry, fluorescence confocal scanning laser microscopy (FCSLM), cell migration assays, ELISAs, functional inhibition studies, metabolic labeling, immunohistochemical analysis, and apoptosis assessment.